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Intestinal organoids as tools for enriching and studying specific and rare cell types:advances and future directions

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Journal of Molecular Cell Biology 2020年第8期12卷 562-568页

作者： Kim E.Boonekamp Talya L.Dayton hans clevers Oncode Institute Hubrecht InstituteRoyal Netherlands Academy of Arts and Sciences(KNAW)and University Medical Centre(UMC)Utrecht358A CT UtrechtThe Netherlands Princess Maxima Centre for Paediatric Oncology 358A CS UtrechtThe Netherlands

Adult tissue-derived organoids allow for the expansion and maintenance of primary epithelial cells in a near-native *** 3D and self-organizing organotypic cultures derived from adult tissues have been increasingly used in fundamental and translational research.A key feature of this organoid system is that it recapitulates the stem cell lineage and thus,the differentiated cell-type heterogeneity of the in vivo tissue of origin.

关键词： directions organo rare

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Wnt-Fzd5 Signaling Directs the Normal Gcml Expression Essential for Placental Branching Morphogenesis

Wnt-Fzd5 Signaling Directs the Normal Gcml Expression Essent...

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2012全国发育生物学大会

作者： Johan H.van Es hans clevers Gustavo Leone State key laboratory of Reproductive Biology Institute of ZoologyChinese Academy of Sciences

Wnt signaling plays an important role in regulating cell proliferation,survival,differentiation,polarization and migration during embryogenesis and is highly conserved from invertebrates to *** study has shown that systemic knockout of Frizzled5(Fzd5),a receptor of Wnt pathway,resulted in placental defects and embryonic lethality by ***,the mechanism underlying the defects remains ***,we show that the initiation of branching in chorion plate could not happen and fetal blood vessels from the allantois failed to penetrate into the chorion,resulting in a dysfunctional labyrinth in the absence of Fzd5 receptors in *** address whether and how trophoblasr-specific depletion of Fzd5 would contribute to the labyrinth developmental defects,we employed multiple approaches,including tetraploid aggregation and CYP19-Cre-mediated trophoblast specific knockout strategies,and demonstrated that Fzd5-deficient embryos supplied with a wild placenta can be carried to a later developmental stage and the process of chorionic branching occurred *** expression of Gcm1,Synb and Cebpa(markers for syncytiotrophoblastⅡ,a trophoblast layer adjacent to fetal vessel endothelial cells) was decreased upon the deletion of Fzd5,suggesting that syncytiotrophoblast development was seriously ***,the expression of tight junction molecule ZO-1,which disappeared at the branching sites in wildtype chorion,still remained at branching sites and the levels of VEGF,which will drive the invasion of fetal blood vessel into the chorion,were decreased in chorion *** addtion,the expression of Gcm 1 was reduced significantly during differentiation of mouse trophoblast stem cells with the deletion of Fzd5 and overexpression of Wnt2,a ligand of Wnt signaling,could increase the expression of Gcm1 during wildtype trophoblast stem cells differentiaton,but not in Fzd5-null trophoblast stem *** suggested that Wnt2-Fzd5 signaling pathway is importan

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Mechanics of serotonin-producing human entero-endocrine cells

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Mechanobiology in Medicine 2024年第2期2卷 55-58页

作者： Tom M.J.Evers Joep Beumer hans clevers Alireza Mashaghi Medical Systems Biophysics and Bioengineering Leiden Academic Centre for Drug ResearchFaculty of ScienceLeiden Universitythe Netherlands Laboratory for Interdisciplinary Medical Innovations Centre for Interdisciplinary Genome ResearchFaculty of ScienceLeiden Universitythe Netherlands Hubrecht Institute Royal Netherlands Academy of Arts and Sciences(KNAW)and UMC UtrechtUtrechtthe Netherlands Oncode Institute Hubrecht InstituteUtrechtthe Netherlands The Princess Maxima Center for Pediatric Oncology Utrechtthe Netherlands Roche Pharmaceutical Research and Early Development BaselSwitzerland

The gastrointestinal(GI)tract's primary role is food digestion,relying on coordinated fluid secretion and bowel movements triggered by *** cells(EECs)are specialized mechanosensitive cells that convert mechanical forces into electrochemical signals,culminating in serotonin release to regulate GI *** their pivotal role,knowledge of EEC mechanical properties has been lacking due to their rarity and limited *** this brief report,we present the first single-cell mechanical characterization of human ECCs isolated from healthy intestinal *** single-cell optical tweezers,we measured EEC stiffness profiles at the physiological temperature and investigated changes following tryptophan metabolism *** findings not only shed light on EEC mechanics but also highlight the potential of adult stem cell-derived organoids for studying these elusive cells.

关键词： Cell mechanics Gut Organoid Serotonin Optical tweezers

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A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta

A positive feedback loop involving Gcm1 and Fzd5 directs cho...

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2012全国发育生物学大会

作者： Haruo Nakano David G.Simmons Johan H.van Es hans clevers Gustavo Leone James C.Cross State key laboratory of Reproductive Biology Institute of ZoologyChinese Academy of Sciences

Chorioallantoic branching morphogenesis is a key milestone during placental development,creating the large surface area for nutrient and gas exchange and is therefore critical for the success of term *** Wnt pathway molecules have been shown to regulate placental ***,it remains largely unknown how Wnt-Frizzled (Fzd) signaling spatiotemporally interacts with other essential regulators,ensuring chorionic branching morphogenesis and angiogenesis during placental *** systemic and trophoblast-specific Fzd5 null and Gcm1 deficient mouse models,combining trophoblast stem cell lines and tetraploid aggregation assay,we demonstrate here that an amplifying signaling loop between Gcm1 and Fzd5 is essential for normal initiation of branching in the chorionic plate. While Gcm1 upregulates Fzd5 specifically at sites where branching initiates in the basal chorion,this elevated Fzd5 expression via nuclearβ-catenin signaling in turn maintains expression of ***,we show that Fzd5-mediated signaling induces the disassociation of cell junctions for branching initiation via downregulating ZO-1 expression in trophoblast cells at the base of the *** addition,Fzd5-mediated signaling is also important for upregulation of Vegf expression in chorion trophoblast ***,we demonstrate that Fzd5-Gcm1 signaling cascade is operative during human trophoblast differentiation. Conclusions:These data indicate that Gcm1 and Fzd5 function in an evolutionary conserved positive feedback loop that regulates trophoblast differentiation and sites of chorionic branching morphogenesis.

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